Control of the release of liquid from a fluidic chamber via a spinning rotor is a very important function in the area of centrifuged-based fluidic systems for applications such as immunoassays, nucleic acid analysis, biochemical tests, chemical tests and sample preparation. This is because it is often necessary to mix different reagents together at the appropriate time, either in parallel or in series.
Solutions to this problem include the use of rotational frequency-dependent burst valves, standard siphons, or mechanical valves. In general, burst valves are less reliable and thus have limited practical applications. As will be described herein, standard siphons (with in between chambers) work reliably but utilize precious space In the radial dimension of a rotor. Mechanical valves of all types necessarily require transduction systems that are complicated and not as reliable as siphons.
Centripetal force is commonly used to move small quantity of liquids into micro-channels (US 2005/0202471 A1; WO 2006/093978 A2). Because centripetal force is not affected by the characteristic of the liquid in terms of pH, salt concentration and to a lesser extent viscosity, it is a valuable force that can be used to move complex liquid samples such as biological samples into micro-channels.
Integration of complex functions on a microfluidic platform requires controllable valves. Most valves used in centripetal fluidic platforms are capillary valves (WO 98/07019). These valves burst at a precise centripetal acceleration applied by the rotor via the rotation of the disk. Valve bursting depends on the geometrical and surface characteristics of the fluidic system. By adjusting and optimizing their geometrical characteristics as well as their surfaces and distances from the center, one can sequentially move liquids from chambers/reservoirs to other chambers/reservoirs. Liquid constraint depends on the G-force applied to the system. When the centripetal G-force is higher than the capillary force, a capillary valve cannot prevent liquid movement within the system.
Some tasks, such as cell lysis and nucleic acid extraction, may require very high centripetal accelerations at the beginning of the protocol. Capillary valves, which are dependent on the G-force, will burst during such high centripetal accelerations. Therefore, capillary valves cannot be used to robustly delay liquid into a downstream chamber in such a system. A way to solve this problem is to use siphon valves. Siphon valves work as follows: An inverted U-shaped channel connects a given upstream dispensing chamber/reservoir to the next downstream receiving chamber/reservoir. The top of the inverted U (or top bend) is oriented toward the center of the rotor (radially inward) and is higher than the level of the liquid present in the upstream chamber. The inverted U-shaped channel has to be hydrophilic and small enough to provide capillary forces. During high centripetal acceleration, the centripetal forces prevent the capillary forces to prime the siphon (i.e. pass the inverted U top level and go lower than the bottom of the upstream chamber). When the centripetal acceleration is decreased below the capillary force, the siphon is primed. After priming, a higher centripetal acceleration will move the liquid from an upstream chamber/reservoir to a downstream chamber/reservoir.
Single siphon valves have been used in centrifugal fluidic devices in applications involving the separation of plasma from whole blood (Scott and Burtis, 1973, Analytical Chemistry, 45:327A-339A). They have also been used as a barrier to ensure the parallel, simultaneous, filling of a series of cuvettes on a rotor (U.S. Pat. No. 5,409,665), as well as in a rotor to transfer a dilution buffer from a holding chamber into a downstream chamber (U.S. Pat. No. 5,693,233). More recently, a rotor comprising siphons for delivering a premeasured volume of liquid between a first and a second chamber was designed (U.S. Pat. No. 6,752,961). This rotor used a sequence of alternating rotations and stops to effect the separation of plasma from whole blood, its dilution, and its distribution into a series of separate reaction cuvettes.